Objectives: The Paced Auditory Serial Addition Test (PASAT) is used to assess cognitive status in multiple sclerosis (MS). Although the mathematical demands of the PASAT seem minor (single-digit arithmetic), cognitive psychology research links greater mathematical ability (e.g., algebra, calculus) to more rapid retrieval of single-digit math facts (e.g., 5+6=11). The present study evaluated the hypotheses that (a) mathematical ability is related to PASAT performance and (b) both the relationship between intelligence and PASAT performance as well as the relationship between education and PASAT performance are both mediated by mathematical ability. Methods: Forty-five MS patients were assessed using the Wechsler Test of Adult Reading, PASAT and Calculation Subtest of the Woodcock-Johnson-III. Regression based path analysis and bootstrapping were used to compute 95% confidence intervals and test for mediation. Results: Mathematical ability (a) was related to PASAT (β=.61; p<.001) and (b) fully mediated the relationship between Intelligence and PASAT (β=.76; 95% confidence interval (CI95)=.28, 1.45; direct effect of Intelligence, β=.42; CI95=−.39, 1.23) as well as the relationship between Education and PASAT (β=2.43, CI95=.81, 5.16, direct effect of Education, β=.83, CI95=−1.95, 3.61). Discussion: Mathematical ability represents a source of error in the clinical interpretation of cognitive decline using the PASAT. Domain-specific cognitive reserve is discussed. (JINS, 2016, 22, 375–378)